In an effort to determine the relative impacts of genetic, socioeconomic- demographic and behavioral-cultural factors on outcome in systemic lupus erythematosus (SLE) among patients from three ethnic groups, we have constituted a cohort of patients with SLE [as per the American College of Rheumatology or (ACR) criteria] of relatively short duration (initially within five years of diagnosis). We have followed this cohort to determine three specific outcomes, disease ACTIVITY, disease DAMAGE, & FUNCTIONING (physical and mental). Thus far, we have obtained and analyzed the data gathered from disease onset to two years into the study. Among our importnt results, we have found that ethnicity, over and above the genetic features examined so far (MHC Class II and III genes and CR1 size and expression polymorphisms) influences disease features and activity early on, whereas later in the course, socioeconomic-demographic features appear to be important modulators of disase activity, damage and functioning; the relationship between disease activity and damage is important, but disease activity over time is significantly influenced by lack of health insurance, helplessness and poor social support; damage does not accrue uniformly across the three ethnic groups but the divergence is just becoming apparent at V2. Finally, despite differences in disease activity and disease damage, self-perceived physical and mental functioning are impaired in a comparable manner in these three ethnic groups. In order to determine the contributions of different variables to the course and outcome of SLE, as the disease progresses and organ damage accumulates, we think it is imperative we extend our observations as well as expand the present cohort to include newly diagnosed patients so that we would have sufficient power to evaluate possible predictive outcome factors for which we did not have sufficient power previously. Our specific aims are thus the following: 1) To continue yearly ascertainment visits of all members of the established LUMINA cohort. 2) To recruit into the LUMINA cohort new patients meeting the same criteria as noted above. 3) To examine additional MHC and non-MHC genetic factors not previously examined to determine their impact on the course and outcome of SLE, specifically TNF, mannose binding protein (MBP), IL-1 receptor antagonist (IL1-RA) and Bcl-2. 4) To refine the assessment of those clinical and behavioral-cultural factors found to be important predictors of disease activity, damage and functioning, thus far. 5) To study the relationships among disease activity, disease damage and physical and mental functioning in these patients as the disease progresses utilizing sophisticated statistical analytical techniques.